A Broader Role For 5ARIs In Prostate Disease? Existing Evidence And Emerging Benefits

Main Category: Prostate / Prostate Cancer
Article Date: 14 Apr 2009 - 1:00 PDT

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UroToday.com - In the online edition of the journal Prostate, Dr. Francesco Montorsi and a group of European colleagues reviewed the expanding use of 5-alpha reductase inhibitors (5ARIs) in prostate diseases. 5ARIs inhibit the conversion of testosterone to dihydrotestosterone (DHT). There are two isoenzymes of 5AR, type 1 and type 2. The 5ARI finasteride is a selective inhibitor of type 2 5AR while dutasteride is a dual 5ARI that inhibits both types 1 and 2.

5ARIs are recommended as a treatment option for men with moderate to severe LUTS secondary to BPH. In addition to improving urinary flow rate and decreasing symptoms, they reduce the risk of acute urinary retention in this population. 5ARIs in combination with alpha-blockers (doxazosin in the MTOPS) trial was superior to either agent as monotherapy. Dutasteride in combination with tamsulosin (CombAT trial) is underway and interim analysis suggests similar superiority to either agent alone.

5ARIs are also indicated for risk reduction for the development of prostate cancer (CaP). The PCPT study demonstrated a 24.8% risk reduction over 7 years in men taking finasteride. The REDUCE trial which tests dutasteride for chemoprevention differs from PCPT in that a negative prostate biopsy is an entry requirement. The relationship between total PSA and free PSA will also be evaluated. One of the underappreciated uses of 5ARIs by physicians is in the detection of prostate cancer; use of a 5ARI is shown to improve the performance of PSA testing. After 12 months of finasteride, one study showed that a smaller decrease in PSA or an increase in PSA was more likely associated with the detection of CaP in men with a previous negative biopsy. A smaller PSA reduction in men taking dutasteride was similarly shown to correlate with the detection of CaP. Doubling of the PSA value in men on 5ARIs is confirmed to effectively correct for the suppression of PSA expression by 5ARIs. This suggests that use of 5ARIs may unmask CaP by preferential suppression of BPH-derived PSA. Interestingly, use of 5ARIs for 2 weeks prior to prostate biopsy is reported to decrease the blood flow to BPH and inflamed prostate tissue on duplex ultrasound, but not to CaP tissue. 5ARIs are also shown to increase the sensitivity of digital rectal examination over time in men in the PCPT trial.

5ARIs are suggested to slow the progression of existing CaP in vitro. Dutasteride has been shown to induce apoptosis in several androgen-sensitive CaP cell lines, but not in castration-resistant cell lines. This may be due to 5ARIs acting as anti-androgens, but has raised some potential concern that 5ARI treatment of CaP may permit a more rapid onset of a castration-resistant state, although this has not been clinically observed.

The authors provided an excellent review of the uses of 5ARIs in the spectrum of prostate diseases.

Montorsi F, Alcaraz A, Desgrandchamps F, Hammerer P, Schröder F, Castro R
Prostate. 2009 Mar 6. Epub ahead of print.
doi:10.1002/pros.20939

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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